RO4929097 and Erlotinib Hydrochloride in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
|ClinicalTrials.gov Identifier: NCT01193881|
Recruitment Status : Terminated
First Posted : September 2, 2010
Last Update Posted : September 29, 2015
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer||Drug: Erlotinib Hydrochloride Drug: Gamma-Secretase Inhibitor RO4929097 Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Addition of the Gamma-Secretase Inhibitor RO4929097 to Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)|
|Study Start Date :||August 2010|
|Primary Completion Date :||August 2015|
|Study Completion Date :||August 2015|
Experimental: Treatment (erlotinib, RO4929097)
Patients receive erlotinib hydrochloride PO QD on days 1-21 and gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO QD on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Erlotinib Hydrochloride
Other Names:Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
- Incidence of adverse events assessed using NCI CTCAE version 4.0 (Dose escalation phase) [ Time Frame: Within 30 days of last drug dose ]
- Maximum-tolerated dose of RO4929097 and erlotinib hydrochloride defined as the highest dose tested causing dose limiting toxicity in < 2/6 patients assessed using National Cancer Institute (NCI) CTCAE version 4.0 (Dose escalation phase) [ Time Frame: At least 3 weeks after day 1 of course 1 ]
- Percentage of change in expression of Notch and other tumor and blood biomarkers (Expansion cohort) [ Time Frame: Baseline to 6 weeks ]The differences before and after treatment will be assessed using a paired-t test on the log-transformed tumor sizes and a Wilcoxon signed-rank test.
- Percentage of tumor shrinkage (Expansion cohort) [ Time Frame: Up to 6 weeks ]Will be correlated with response and baseline expression of biomarkers. The differences before and after treatment will be assessed using a paired-t test on the log-transformed tumor sizes and a Wilcoxon signed-rank test.
- Response rate by RECIST 1.1 (Expansion cohort) [ Time Frame: Up to 12 weeks ]
- Time to progression (Expansion cohort) [ Time Frame: Up to 12 weeks ]Will be correlated with baseline expression or biomarkers.
- Efficacy of this combination in unselected patients and in patients with intrinsic or acquired erlotinib resistance (Dose escalation phase) [ Time Frame: Up to 12 weeks ]
- Host Notch pathway gene polymorphisms [ Time Frame: Up to 6 weeks ]Correlations between Notch pathway gene polymorphisms and tumor and blood biomarkers will be assessed. Correlations between Notch pathway gene polymorphisms and tumor shrinkage/response on therapy will also be assessed.
- Pre-therapy tumor expression of Notch and other tumor and blood biomarkers (Dose escalation phase) [ Time Frame: Baseline ]Exploratory assessments of correlations of tumor shrinkage and response on the combination with pre-therapy tumor expression of Notch and other tumor and blood biomarkers will be conducted.
- Stem cell markers [ Time Frame: Up to 6 weeks ]Correlations between Notch pathway markers and stem cell markers will be assessed.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01193881
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Don Gibbons||M.D. Anderson Cancer Center|